Zavesca

miglustat

This is a summary of the European public assessment report (EPAR) for Zavesca. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Zavesca.

What is Zavesca?

Zavesca is a medicine that contains the active substance miglustat. It is available as white capsules (100 mg).

What is Zavesca used for?

Zavesca is used to treat two inherited diseases that affect the way the body handles fats. Both diseases cause a build-up of fatty substances called glycosphingolipids in the body. Zavesca is used in the following patients:

• adults (aged 18 years or over) with mild to moderate type-1 Gaucher disease. Patients with this disease lack an enzyme called glucocerebrosidase, which results in a glycosphingolipid called glucosylceramide building up in different parts of the body, such as the spleen, liver and bones. Zavesca is used in patients who cannot receive the standard treatment of enzyme replacement therapy (ERT) given by infusion (drip into a vein);
• patients of all ages with Niemann-Pick-type-C disease, a potentially fatal disease in which glycosphingolipids build up within cells in the brain and elsewhere in the body. Zavesca is used to treat the neurological symptoms of the disease (symptoms affecting the brain and nerves). These include loss of co-ordination, problems with ‘saccadic’ (rapid) eye movements that can lead to impaired vision, delayed development, difficulty swallowing, increased muscle tone, fits and learning difficulties.

Because the number of patients with these diseases is low, they are considered ‘rare’, and Zavesca was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 18 October 2000 for type-1 Gaucher disease and on 16 February 2006 for Niemann-Pick-type-C disease.

The medicine can only be obtained with a prescription.

How is Zavesca used?

Treatment with Zavesca should be started and monitored by doctors who are experienced in the management of Gaucher or Niemann-Pick-type-C disease.

The recommended starting dose for type-1 Gaucher disease is one capsule three times a day. For Niemann-Pick-type-C disease, it is two capsules three times a day for patients aged 12 years and over; in younger patients, the dose depends on their weight and height. Zavesca is intended for long-term use.

A lower dose should be used in patients with kidney problems. The dose should also be reduced temporarily in patients who develop diarrhoea. For further information, see the summary of product characteristics (also part of the EPAR).

How does Zavesca work?

The active substance in Zavesca, miglustat, prevents an enzyme called glucosylceramide synthase from working. This enzyme is involved in the first step of the production of glycosphingolipids. By preventing the enzyme from working, miglustat can reduce the production of glycosphingolipids in cells. This is expected to slow down or prevent the development of the symptoms of type-1 Gaucher disease and to reduce the symptoms of Niemann-Pick-type-C disease.

How has Zavesca been studied?

For type-1 Gaucher disease, Zavesca was investigated in one main study involving 28 adults with mild to moderate disease who were unable or unwilling to receive ERT. The main part of the study lasted for a year, but 13 patients carried on receiving the medicine for a further two years. The study looked at the effect of Zavesca on the size of the liver and spleen, and at blood counts, such as the levels of haemoglobin (a protein found in red blood cells that carries oxygen around the body) and platelets (components that help the blood to clot).

For Niemann-Pick-type-C disease, Zavesca was studied in one main study involving 31 patients, 12 of whom were less than 12 years old. The study compared the effects of adding Zavesca to standard care with the effects of standard care alone. The main measure of effectiveness was the change in the speed at which the patients made saccadic horizontal eye movements after a year, but the study also looked at other neurological symptoms such as the patients’ ability to swallow and their intellectual function. Some patients were treated for up to five and a half years. The company also presented the results of a survey of 66 patients treated with Zavesca.

What benefit has Zavesca shown during the studies?

In the study of type-1 Gaucher disease, there were moderate reductions in the size of the liver (12% reduction) and the spleen (19% reduction) after a year. There were also small improvements in blood counts: on average, the levels of haemoglobin increased by 0.26 g per decilitre and platelet counts increased by 8.29 million per millilitre. The benefits of Zavesca were maintained over three years of continuous treatment.

In the study of Niemann-Pick-type-C disease, the improvement in eye movements was similar in patients treated with and without Zavesca. However, there were signs of improvement in swallowing ability and intellectual function in the patients treated with Zavesca. The survey showed that Zavesca led to a stabilisation or a decrease in the rate at which symptoms got worse in about three quarters of the patients.

What is the risk associated with Zavesca?

The most common side effects with Zavesca (seen in more than 1 patient in 10) are weight loss, tremor (shaking), diarrhoea, flatulence (gas) and abdominal pain (stomach ache). For the full list of all side effects reported with Zavesca, see the package leaflet.

Zavesca should not be used in people who may be hypersensitive (allergic) to miglustat or any of the other ingredients.

Why has Zavesca been approved?

The CHMP decided that Zavesca’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Zavesca has been authorised under ‘exceptional circumstances’ because, as the diseases are rare, it has not been possible to obtain complete information on the medicine. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Zavesca?

The company that makes Zavesca will complete the following studies to address the product’s effectiveness and safety in type-1 Gaucher disease:

• a post-marketing surveillance plan to inform doctors on how to use Zavesca and to get patients to report information on the safety of the medicine;
• a study to look at the effectiveness and safety of Zavesca in patients who switch from ERT;
• a further study of the natural history of the disease, together with the European Working Group for Gaucher Disease (EWGGD).

Other information about Zavesca

The European Commission granted a marketing authorisation valid throughout the European Union for Zavesca on 20 November 2002. The marketing authorisation holder is Actelion Registration Ltd. After five years, the marketing authorisation was renewed for a further five years.

For more information about treatment with Zavesca, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 26/03/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

01/02/2013  Zavesca -EMEA/H/C/000435 -IB/040G

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Other alimentary-tract and metabolism products

Therapeutic indication

Zavesca is indicated for the oral treatment of adult patients with mild to moderate type-1 Gaucher disease. Zavesca may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable.

Zavesca is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with Niemann-Pick-type-C disease.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents